Synapses are key elements of communication and signal processing in the healthy brain. Furthermore, synapses are severely perturbed in several neurological and psychiatric diseases. This proposal requests support for an international Gordon Research Conference (GRC) on Synaptic Transmission in 2014 and a corresponding inaugural Gordon Research Seminar (GRS), to be held at the Waterville Valley Resort, New Hampshire, during the week of August 2-8, 2014. We plan to bring together a group of scientists who all are highly interested in synaptic function, but examine synapses at different levels (molecular, cellular, and systems level), look at them from different perspectives (bottom-up, top-down), and use different approaches (molecular biology, imaging, optogenetics, subcellular electrophysiology, modeling, and many others). The long-term objectives of the conference series are (1) to increase our understanding of the fundamental molecular and cellular mechanisms of synaptic transmission, (2) to elucidate how synaptic transmission shapes neuronal network activity, and (3) to link basic science on synapses to disease aspects. The specific aims are (1) to include a new focus on subcellular analysis, connectomics, and synaptic transmission in vivo, (2) to enhance the contribution of students, postdocs, and young faculty members, and (3) to achieve the highest possible scientific quality, while further optimizing the balance of gender, age, and nationality at all levels (speakers, discussion leaders, and short talk presenters). We envisage having ~34 speakers representing critical areas of synaptic transmission research with a maximum of 200 participants for an intense five day conference in a retreat-like setting. The program will have two Keynote Lectures entitled Synaptic transmission: from molecular machines to network activity and eight sessions that address different aspects of synaptic signaling, including mechanisms of exocytosis, presynaptic terminals, synaptic spines, pre- and postsynaptic plasticity, connectomics, synaptic diseases, and function of synapses in microcircuits and neuronal networks in vivo. Short talks sessions and evening poster sessions on all four days will permit all participants to contribute to these topics. The health and disease relevance of this application is substantial. Although many presentations will focus on basic science, the presented data have far-reaching implications for a wide range of devastating brain disorders, particularly neurodegenerative diseases such as Parkinson's and Alzheimer's disease, mood disorders, schizophrenia, autism spectrum disorders, mental retardation, drug addiction, and loss of peripheral sensory function, which are collectively emerging as synaptopathies. Thus, we are convinced that the results presented at this meeting will help clinical researchers to develop new therapeutic strategies for major brain diseases. We anticipate that the GRC Synaptic Transmission will have a major shaping influence on both basic and disease-related neuroscience in the next decade.